ArticleProceedings of the National Academy of Sciences of the United States of America2013
Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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23 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
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- Chromosome-level genome of Neodon fuscus sheds light on the evolution and plateau adaptation of N. fuscus and Neodon.BMC genomics · 2025Article
- Convergent TP53 loss and evolvability in cancer.BMC ecology and evolution · 2023Review
- The influence of meteorological factors and total malignant tumor health risk in Wuhu city in the context of climate change.BMC public health · 2023Article
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- Response to Different Oxygen Partial Pressures and Evolution Analysis of Apoptosis-Related Genes in Plateau Zokor (Frontiers in genetics · 2022Article
- The hypoxia adaptation of small mammals to plateau and underground burrow conditions.Animal models and experimental medicine · 2021Review
- Beyond history and "on a roll": The list of the most well-studied human protein structures and overall trends in the protein data bank.Protein science : a publication of the Protein Society · 2021Review
- Ongoing selection for a uniquely human null allele ofFASEB bioAdvances · 2021Article
- Broadening the spectrum of cancer genes under selection in human populations.FASEB bioAdvances · 2021Article
- The untapped potential of reptile biodiversity for understanding how and why animals age.Functional ecology · 2020Article
- Antagonistic Pleiotropy in Human Disease.Journal of molecular evolution · 2020Review
- Functional Diversity of p53 in Human and Wild Animals.Frontiers in endocrinology · 2019Review
- Migration-Selection Balance Drives Genetic Differentiation in Genes Associated with High-Altitude Function in the Speckled Teal (Anas flavirostris) in the Andes.Genome biology and evolution · 2018Article
- The double benefit of Spalax p53: surviving underground hypoxia while defying lung cancer cells in vitro via autophagy and caspase-dependent cell death.Oncotarget · 2016Article
- Adaptive methylation regulation of p53 pathway in sympatric speciation of blind mole rats, Spalax.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
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13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutational changes in p53 correlate well with tumorigenesis. Remarkably, however, relatively little is known about the role that p53 variations may play in environmental adaptation. Here we report that codon asparagine-104 (104N) and glutamic acid-104 (104E), respectively, of the p53 gene in the wild zokor (Myospalax baileyi) and root vole (Microtus oeconomus) are adaptively variable, meeting the environmental stresses of the Tibetan plateau. They differ from serine-104 (104S) seen in other rodents, including the lowland subterranean zokor Myospalax cansus, and from serine 106 (106S) in humans. Based on site-directed mutational analysis in human cell lines, the codon 104N variation in M. baileyi is responsible for the adaptive balance of the transactivation of apoptotic genes under hypoxia, cold, and acidic stresses. The 104E p53 variant in Microtus oeconomus suppresses apoptotic gene transactivation and cell apoptosis. Neither 104N nor 104E affects the cell-cycle genes. We propose that these variations in p53 codon 104 are an outcome of environmental adaptation and evolutionary selection that enhance cellular strategies for surviving the environmental stresses of hypoxia and cold (in M. baileyi and M. oeconomus) and hypercapnia (in M. baileyi) in the stressful environments of the Qinghai-Tibet plateau.
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